title: Time resolved study of cell death mechanisms induced by amine-modified polystyrene nanoparticles.
abstract: Positively charged polymers and nanoparticles (NPs) can be toxic to cells in various systems. Using human astrocytoma cells, we have previously shown that 50 nm amine-modified polystyrene NPs damage mitochondria and induce cell death by apoptosis. Here we provide comprehensive details of the cellular events occurring after exposure to the NPs in a time-resolved manner. We demonstrate that the accumulation of NPs in lysosomes plays a central role in the observed cell death, leading to swelling of the lysosomes and release of cathepsins into the cytosol, which ultimately propagates the damage to the mitochondria with subsequent activation of apoptosis. This is accompanied and sustained by other events, such as increasing ROS levels and autophagy. Using various inhibitors, we also show the interplay between apoptosis and autophagy as a response to NP accumulation in lysosomes.
authors.affiliation: Centre for BioNano Interactions and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. Kenneth.A.Dawson@cbni.ucd.ie Anna.Salvati@cbni.ucd.ie.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Wang
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Bexiga
authors.forename: Sergio
authors.initials: S
authors.lastname: Anguissola
authors.forename: Patricia
authors.initials: P
authors.lastname: Boya
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Simpson
authors.forename: Anna
authors.initials: A
authors.lastname: Salvati
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
mesh_terms: D000588:Amines / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010718:Phosphatidylserines / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D000588:Amines; D010718:Phosphatidylserines; D011137:Polystyrenes; D017382:Reactive Oxygen Species